Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

• Type of Material: Article
• Authors: Mariam B. Gonzalez-Hernandez, University of Michigan; Thomas Liu, University of Michigan; Hilary C. Payne, University of Michigan; Jennifer E. Stencel-Baerenwald, Vanderbilt University; Mine Ikizler, Vanderbilt University; Hideo Yagita, Juntendo University; Terence S. Dermody, Vanderbilt University; Ifor Williams, Emory University; Christiane E. Wobus, University of Michigan
• Language: English
• Date: 2014-06
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.00204-14
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 88
• Issue: 12
• Start Page: 6934
• End Page: 6943
• Grant/Funding Information: H.Y. was funded by a grant-in-aid (S1201013) from the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2012 to 2017.; Additional funding was provided by Public Health Service award R37 AI38296 and the Elizabeth B. Lamb Center for Pediatric Research to T.S.D. and Public Health Service awards CA68485 for the Vanderbilt-Ingram Cancer Center and DK20593 for the Vanderbilt Diabetes Research and Training Center.; This work was funded by start-up funds from the University of Michigan and NIH grants AI080611; and AI103961 to C.E.W. M.B.G.-H. was funded by a University of Michigan Experimental Immunology Training Grant (NIH T32 A1007413-16), a Molecular Mechanisms of Microbial Pathogenesis Training Grant (NIH T32 A1007528), and the Herman and Dorothy Miller Fund for Innovative Immunology Research.; I.R.W. was funded by NIH R01 DK64730.
• Keywords: Science & Technology; EPITHELIAL M-CELLS; REVERSE GENETICS; PEYERS-PATCHES; SIALIC-ACID; MICROBIAL PATHOGENESIS; PATCH DENDRITIC CELLS; ATTACHMENT RECEPTORS; Virology; SALMONELLA-TYPHIMURIUM; SHIGELLA-FLEXNERI; MURINE NOROVIRUS; VIROLOGY; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Microbiology

Abstract

Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. Mcells have also been suggested as a portal for pathogen entry into the host. While virus particles have been observed in Mcells, it is not known whether viruses useMcells to initiate a productive infection. Noroviruses (NoVs) are single-stranded RNA viruses that infect host organisms via the fecal-oral route. Murine NoV (MNV) infects intestinal macrophages and dendritic cells and provides a tractable experimental system for understanding how an enteric virus overcomes the intestinal epithelial barrier to infect underlying target cells. We found that replication of two divergent MNV strains was reduced in mice depleted ofMcells. Reoviruses are double-stranded RNA viruses that infect hosts via respiratory or enteric routes. In contrast to MNV, reovirus infects enterocytes in the intestine. Despite differences in cell tropism, reovirus infection was also reduced inMcell-depleted mice. These data demonstrate thatMcells are required for the pathogenesis of two unrelated enteric viruses that replicate in different cell types within the intestine.